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Viruses Feb 2024The co-occurrence of human immunodeficiency virus (HIV) and tuberculosis (TB) infection poses a significant global health challenge. Treatment of HIV and TB co-infection... (Review)
Review
The co-occurrence of human immunodeficiency virus (HIV) and tuberculosis (TB) infection poses a significant global health challenge. Treatment of HIV and TB co-infection often necessitates combination therapy involving antiretroviral therapy (ART) for HIV and anti-TB medications, which introduces the potential for drug-drug interactions (DDIs). These interactions can significantly impact treatment outcomes, the efficacy of treatment, safety, and overall patient well-being. This review aims to provide a comprehensive analysis of the DDIs between anti-HIV and anti-TB drugs as well as potential adverse effects resulting from the concomitant use of these medications. Furthermore, such findings may be used to develop personalized therapeutic strategies, dose adjustments, or alternative drug choices to minimize the risk of adverse outcomes and ensure the effective management of HIV and TB co-infection.
Topics: Humans; Coinfection; HIV; Tuberculosis; HIV Infections; Drug Interactions; Anti-HIV Agents
PubMed: 38543687
DOI: 10.3390/v16030321 -
Pulmonary Pharmacology & Therapeutics Dec 2023Longitudinal epidemiological and clinical data are needed to improve the management of patients with bronchiectasis developing nontuberculous mycobacterial (NTM)...
RATIONALE
Longitudinal epidemiological and clinical data are needed to improve the management of patients with bronchiectasis developing nontuberculous mycobacterial (NTM) pulmonary disease.
OBJECTIVES
To describe the epidemiology, patient management, and treatment outcomes of NTM infections in patients with bronchiectasis enrolled in the United States Bronchiectasis and NTM Research Registry (US BRR).
METHODS
This was a retrospective cohort study of patients with bronchiectasis and NTM infections enrolled with follow-up in the US BRR in 2008-2019. The study included patients with ≥1 positive NTM respiratory culture in the 24-month baseline period (baseline NTM cohort) and/or during the annual follow-up visits (incident NTM cohort). Incidence, prevalence, baseline patient characteristics, treatment exposure, treatment outcomes, and respiratory clinical outcomes were described in the baseline NTM cohort, incident NTM cohort, and both cohorts combined (prevalent NTM cohort).
RESULTS
Between 2008 and 2019, 37.9% (1457/3840) of patients with bronchiectasis in the US BRR met the inclusion criteria for this study and were reported to have Mycobacterium avium complex (MAC) and/or Mycobacterium abscessus complex (MABSC) infections. MAC prevalence increased steadily in the US BRR during 2009-2019; incidence was relatively stable, except for a peak in 2011 followed by a slow decrease. MABSC and mixed MAC/MABSC infections were rare. Most patients with bronchiectasis and NTM infections in the registry were female, White, and aged >65 years. The antibiotics administered most commonly reflected current guidelines. In the prevalent cohort, 44.9% of MAC infections and 37.1% of MABSC infections remained untreated during follow-up, and MAC treatment was initiated with delay (>90 days after positive NTM respiratory culture) twice as frequently as promptly (≤90 days after positive NTM respiratory culture) (68.6% vs 31.4%, respectively). The median time from diagnosis to treatment was shorter for MABSC versus MAC infections (194.0 days [interquartile range (IQR) 8.0, 380.0] vs 296.0 days [IQR 35.0, 705.0], respectively). Among patients with MAC infections who completed treatment, 27.6% were classified as cured and 29.6% as treatment failure during the annual follow-up visit window. For MABSC, these proportions were 25.0% and 28.0%, respectively.
CONCLUSIONS
A considerable proportion of MAC and MABSC infections were untreated or treated after initial delay/observation. MABSC infections were more likely to be treated and start treatment sooner than MAC infections. Further longitudinal studies are warranted to evaluate the monitor-with-delay approach and inform clinical guidelines.
Topics: Humans; Female; Male; Retrospective Studies; Cohort Studies; Mycobacterium Infections, Nontuberculous; Nontuberculous Mycobacteria; Mycobacterium avium Complex; Bronchiectasis; Registries
PubMed: 37741357
DOI: 10.1016/j.pupt.2023.102260 -
BMC Immunology Jul 2023Understanding the complex interactions of the immune response mediated by Mycobacterium tuberculosis and HIV co-infection is fundamental to disease biomarker discovery,...
BACKGROUND
Understanding the complex interactions of the immune response mediated by Mycobacterium tuberculosis and HIV co-infection is fundamental to disease biomarker discovery, vaccine, and drug development. Using flow cytometry, we characterized the frequencies and phenotypic differences in monocytes and dendritic cell populations using peripheral blood mononuclear cells from individuals with recurrent, active pulmonary tuberculosis with and without coexisting HIV infection (CAPRISA 011, Clinicaltrials.gov, NCT02114684, 29/01/2014) and compared them to samples from HIV positive individuals and healthy controls. Additionally, we assessed the associations between the frequency of monocyte and dendritic cell subsets and time to culture conversion and cavitary disease in patients with active TB using a cox proportional hazards and logistic regression models.
RESULTS
Compared to healthy controls, the frequency of total monocytes (HLA-DR + CD14 +) was significantly higher in the TB/HIV and TB groups and the frequency of dendritic cells (HLA-DR + CD14-) was significantly higher in TB/HIV and HIV groups. We observed significant variation in the expression of CCR2, CD40, CD11b, CD86, CD163, CX3CR1 across different cell subsets in the four study groups. Increase in CCR2, CD11b and CD40 was associated with active TB infection, while decrease in CX3CR1 and increase in CD163 was associated with HIV infection. Expression of CX3CR1 (aHR 0.98, 95% CI 0.963 - 0.997, p = 0.019) on non-classical monocytes associated with longer time to TB culture conversion in the multivariable model correcting for randomization arm, age, sex, HIV status, lung cavitation, alcohol use, smoking and BMI. Higher surface expression of CD86 (aOR 1.017, 95% CI 1.001 - 1.032, p = 0.033) on intermediate monocytes associated with the presence of lung cavitation, while higher expression of transitional monocytes (aOR 0.944, 95% CI 0.892 - 0.999, p = 0.047) associated with the absence of lung cavitation in the multivariable model.
CONCLUSION
These data provide valuable insight into the heterogenous role of monocyte and dendritic cells in TB and HIV infections.
Topics: Humans; Monocytes; Mycobacterium tuberculosis; HIV Infections; Leukocytes, Mononuclear; Coinfection; Tuberculosis; CD40 Antigens; Dendritic Cells
PubMed: 37480005
DOI: 10.1186/s12865-023-00558-z -
The Journal of Infectious Diseases Aug 2023Nontuberculous mycobacteria (NTM) are ubiquitous in the environment and an increasingly frequent cause of opportunistic infections. Mycobacterium abscessus complex...
BACKGROUND
Nontuberculous mycobacteria (NTM) are ubiquitous in the environment and an increasingly frequent cause of opportunistic infections. Mycobacterium abscessus complex (MABC) is one of the major NTM lung pathogens that disproportionately colonize and infect the lungs of individuals with cystic fibrosis (CF). MABC infection can persist for years, and antimicrobial treatment is frequently ineffective.
METHODS
We sequenced the genomes of 175 isolates longitudinally collected from 30 patients with MABC lung infection. We contextualized our cohort amidst the broader MABC phylogeny and investigated genes undergoing parallel adaptation across patients. Finally, we tested the phenotypic consequences of parallel mutations by conducting antimicrobial resistance and mercury-resistance assays.
RESULTS
We identified highly related isolate pairs across hospital centers with low likelihood of transmission. We further annotated nonrandom parallel mutations in 22 genes and demonstrated altered macrolide susceptibility co-occurring with a nonsynonymous whiB1 mutation. Finally, we highlighted a 23-kb mercury-resistance plasmid whose loss during chronic infection conferred phenotypic susceptibility to organic and nonorganic mercury compounds.
CONCLUSIONS
We characterized parallel genomic processes through which MABC is adapting to promote survival within the host. The within-lineage polymorphisms we observed have phenotypic effects, potentially benefiting fitness in the host at the putative detriment of environmental survival.
Topics: Humans; Mycobacterium abscessus; Clarithromycin; Host Adaptation; Mycobacterium Infections, Nontuberculous; Anti-Bacterial Agents; Genomics
PubMed: 37254795
DOI: 10.1093/infdis/jiad187 -
Frontiers in Immunology 2023() and SARS-CoV-2 are both infections that can lead to severe disease in the lower lung. However, these two infections are caused by very different pathogens ( virus),... (Review)
Review
() and SARS-CoV-2 are both infections that can lead to severe disease in the lower lung. However, these two infections are caused by very different pathogens ( virus), they have different mechanisms of pathogenesis and immune response, and differ in how long the infection lasts. Despite the differences, SARS-CoV-2 and share a common feature, which is also frequently observed in other respiratory infections: the burden of disease in the elderly is greater. Here, we discuss possible reasons for the higher burden in older adults, including the effect of co-morbidities, deterioration of the lung environment, auto-immunity, and a reduced antibody response. While the answer is likely to be multifactorial, understanding the main drivers across different infections may allow us to design broader interventions that increase the health-span of older people.
Topics: Humans; Aged; COVID-19; SARS-CoV-2; Tuberculosis; Mycobacterium tuberculosis; Cost of Illness
PubMed: 37841265
DOI: 10.3389/fimmu.2023.1250198 -
International Journal of Molecular... Aug 2023Tuberculosis (TB) remains an important public health problem and one of the leading causes of death. Individuals with latent tuberculosis infection (LTBI) have an... (Review)
Review
Tuberculosis (TB) remains an important public health problem and one of the leading causes of death. Individuals with latent tuberculosis infection (LTBI) have an increased risk of developing active TB. The problem of the diagnosis of the various stages of TB and the identification of infected patients in the early stages has not yet been solved. The existing tests (the tuberculin skin test and the interferon-gamma release assay) are useful to distinguish between active and latent infections. But these tests cannot be used to predict the development of active TB in individuals with LTBI. The purpose of this review was to analyze the extant data of the interaction of with immune cells and identify molecular predictive markers and markers of the early stages of TB. An analysis of more than 90 sources from the literature allowed us to determine various subpopulations of immune cells involved in the pathogenesis of TB, namely, macrophages, dendritic cells, B lymphocytes, T helper cells, cytotoxic T lymphocytes, and NK cells. The key molecular markers of the immune response to are cytokines (IL-1β, IL-6, IL-8, IL-10, IL-12, IL-17, IL-22b, IFNɣ, TNFa, and TGFß), matrix metalloproteinases (MMP-1, MMP-3, and MMP-9), and their inhibitors (TIMP-1, TIMP-2, TIMP-3, and TIMP-4). It is supposed that these molecules could be used as biomarkers to characterize different stages of TB infection, to evaluate the effectiveness of its treatment, and as targets of pharmacotherapy.
Topics: Humans; Precision Medicine; Tuberculosis; Latent Tuberculosis; Mycobacterium tuberculosis; Biomarkers; Immunity
PubMed: 37686061
DOI: 10.3390/ijms241713261 -
The American Journal of Tropical... Jul 2023Mycobacterium tuberculosis and HIV constitute a public health challenge. Health workers (HWs) in HIV clinics maybe at greater risk of M. tuberculosis infection,...
Mycobacterium tuberculosis and HIV constitute a public health challenge. Health workers (HWs) in HIV clinics maybe at greater risk of M. tuberculosis infection, considering the high rates of HIV/tuberculosis (TB) coinfection among patients. Hence, we measured the prevalence of M. tuberculosis infection and the effect of working in an HIV clinic. We conducted a cross-sectional study in high-HIV burden health-care facilities in Abuja and Nasarawa states and recruited HWs over 4 months. We administered questionnaires and screened for M. tuberculosis infection using QuantiFERON-TB Gold-Plus. A total of 1,043 HWs were enrolled, with the majority being clinical staff (77.4%). Prevalence of interferon gamma release assay (IGRA) positivity was 44.8% (43.8% among HWs from HIV clinic and 45.3% from non-HIV clinics, P = 0.24). Nonoccupational factors such as living in a moderately (odds ratio [OR] = 0.71] or sparsely populated neighborhood (OR = 0.56), remained associated with a reduced risk of IGRA positivity, whereas male gender (OR = 1.37) and having high blood pressure (HBP) (OR = 1.52) remained associated with an increased risk after adjusting. Occupational factors such as length of career as a HW of 10 to 20 years (OR = 1.45) or 20 to 30 years (OR = 1.74) remained associated with an increased risk of IGRA positivity after adjusting. In a final multivariate model, the factors of age between 20 to < 30 years (OR = 0.61), having HBP (OR = 1.56), having a length of career as a HW of 10 to 20 years (OR = 1.66) or 20 to 30 years (OR = 2.09) and being a clinical HW (OR = 0.62) remained associated with IGRA positivity. There is a high prevalence of IGRA positivity among HWs in Nigeria. Working in HIV clinics, however, is not associated with increased risk.
Topics: Humans; Male; Young Adult; Adult; Latent Tuberculosis; Interferon-gamma Release Tests; Prevalence; Cross-Sectional Studies; Nigeria; Tuberculosis; Risk Factors; Mycobacterium tuberculosis; HIV Infections; Tuberculin Test
PubMed: 37253444
DOI: 10.4269/ajtmh.22-0531 -
Microbiology Spectrum Aug 2023Mycobacterium abscessus, an intracellular nontuberculous mycobacterium, is considered the most pathogenic species among the group of rapidly growing mycobacteria. The...
Mycobacterium abscessus, an intracellular nontuberculous mycobacterium, is considered the most pathogenic species among the group of rapidly growing mycobacteria. The resistance of M. abscessus to the host innate response contributes to its pathogenicity in addition to several virulence factors. We have recently shown in that antimicrobial peptides (AMPs), whose production is induced by M. abscessus, are unable to control mycobacterial infection. This could be due to their inability to kill mycobacteria and/or the hidden location of the pathogen in phagocytic cells. Here, we demonstrate that the rapid internalization of M. abscessus by macrophages allows it to escape the AMP-mediated humoral response. By depleting phagocytes in AMP-deficient flies, we found that several AMPs were required for the control of extracellular M. abscessus. This was confirmed in the Tep4 opsonin-deficient flies, which we show can better control M. abscessus growth and have increased survival through overproduction of some AMPs, including Defensin. Furthermore, Defensin alone was sufficient to kill extracellular M. abscessus both and and control its infection. Collectively, our data support that Tep4-mediated opsonization of M. abscessus allows its escape and resistance toward the Defensin bactericidal action in . Mycobacterium abscessus, an opportunistic pathogen in cystic fibrosis patients, is the most pathogenic species among the fast-growing mycobacteria. How M. abscessus resists the host innate response before establishing an infection remains unclear. Using , we have recently demonstrated that M. abscessus resists the host innate response by surviving the cytotoxic lysis of the infected phagocytes and the induced antimicrobial peptides (AMPs), including Defensin. In this work, we demonstrate that M. abscessus resists the latter response by being rapidly internalized by phagocytes. Indeed, by combining and approaches, we show that Defensin is able to control extracellular M. abscessus infection through a direct bactericidal action. In conclusion, we report that M. abscessus escapes the host AMP-mediated humoral response by taking advantage of its internalization by the phagocytes.
Topics: Animals; Mycobacterium abscessus; Drosophila; Opsonization; Mycobacterium; Antimicrobial Peptides; Defensins; Mycobacterium Infections, Nontuberculous; Anti-Bacterial Agents
PubMed: 37260399
DOI: 10.1128/spectrum.00777-23 -
Tuberculosis (Edinburgh, Scotland) Jul 2024Tuberculosis, caused by Mycobacterium tuberculosis, remains one of the deadliest infections in humans. Because Mycobacterium bovis Bacillus Calmette-Guérin (BCG) share...
Tuberculosis, caused by Mycobacterium tuberculosis, remains one of the deadliest infections in humans. Because Mycobacterium bovis Bacillus Calmette-Guérin (BCG) share genetic similarities with Mycobacterium tuberculosis, it is often used as a model to elucidate the molecular mechanisms of more severe tuberculosis infection. Caveolin-1 has been implied in many physiological processes and diseases, but it's role in mycobacterial infections has barely been studied. We isolated macrophages from Wildtype or Caveolin-1 deficient mice and analyzed hallmarks of infection, such as internalization, induction of autophagy and apoptosis. For in vivo assays we intravenously injected mice with BCG and investigated tissues for bacterial load with colony-forming unit assays, bioactive lipids with mass spectrometry and changes of protein expressions by Western blotting. Our results revealed that Caveolin-1 was important for early killing of BCG infection in vivo and in vitro, controlled acid sphingomyelinase (Asm)-dependent ceramide formation, apoptosis and inflammatory cytokines upon infection with BCG. In accordance, Caveolin-1 deficient mice and macrophages showed higher bacterial burdens in the livers. The findings indicate that Caveolin-1 plays a role in infection of mice and murine macrophages with BCG, by controlling cellular apoptosis and inflammatory host response. These clues might be useful in the fight against tuberculosis.
Topics: Animals; Caveolin 1; Apoptosis; Mycobacterium bovis; Mice, Knockout; Mice, Inbred C57BL; Macrophages; Tuberculosis; Sphingomyelin Phosphodiesterase; Autophagy; Host-Pathogen Interactions; Disease Models, Animal; Bacterial Load; Cytokines; Ceramides; Liver; Cells, Cultured; Mice; Inflammation Mediators; Time Factors
PubMed: 38547568
DOI: 10.1016/j.tube.2024.102493 -
PloS One 2023It has been reported that the risk of mental health problems such as anxiety or depression increases in patients with nontuberculous mycobacterial (NTM) infection....
BACKGROUND
It has been reported that the risk of mental health problems such as anxiety or depression increases in patients with nontuberculous mycobacterial (NTM) infection. However, no studies have investigated whether the incidence of NTM infection increases in patients with depression. This study aimed to investigate the incidence of NTM infection in patients with depression and evaluate the association between NTM infection and depression stratified by age and sex.
METHODS
Data from 2002 to 2013 were collected from patients aged ≥ 20 years in the National Health Insurance Service-National Sample Cohort database. Patients with and without depression aged over 20 years were matched with 1 to 4 by sex, age, and year of diagnosis. The incidence rate was calculated in 100,000 person-years, and a multivariable subdistribution hazard model was used to evaluate the adjusted hazard ratio (aHR) for the development of NTM infection.
RESULTS
We included 37,554 individuals (12,752 men and 24,802 women) and 149,213 controls in the depression and non-depression groups, respectively. The cumulative incidence of NTM infection did not differ significantly between the depression and non-depression groups during the follow-up period (22.2 vs. 24.5 per 100,000 person-years, p = 0.571). The age- and sex-stratified effects on the incidence of NTM infection were not significantly higher in patients with depression than in those without depression. After adjusting for covariates including age, sex, comorbidity, income, and region, the risk of NTM infection did not significantly differ between the depression and non-depression groups (aHR 0.83, 95% confidence interval 0.58-1.17).
CONCLUSION
The incidence of NTM infections in patients with depression was not significantly higher than that in patients without depression. However, due to the small number of NTM infections, we might have underestimated the differences between the two groups. Further studies are needed to identify factors associated with NTM pulmonary disease in patients with depression.
Topics: Male; Humans; Female; Adult; Incidence; Patients; Anxiety; Anxiety Disorders; Mycobacterium Infections, Nontuberculous; Risk Factors
PubMed: 37590304
DOI: 10.1371/journal.pone.0290271